SRPX (sushi repeat-containing protein X-linked) is an extracellular matrix protein with emerging roles in cancer progression and tumor microenvironment signaling. Mechanistically, SRPX functions through multiple pathways: it interacts with cytoskeletal proteins including PELO, HAX1, and EIF3G at actin microfilaments 1, and regulates cancer-associated fibroblast (CAF) biology via RhoA signaling to promote ovarian cancer invasiveness 2. In glioma, SRPX mutations (p.L14DEL and p.L23DEL) drive malignant progression by promoting AHR-mediated transcriptional upregulation, activating the EGFR/Akt/Nestin pathway and enhancing cancer stem cell properties 3. SRPX has been identified as a hub gene in CAF-associated prognostic signatures for ovarian cancer 4 and clear cell renal cell carcinoma 5, where high expression correlates with poor prognosis and immunosuppressive microenvironments. Clinically, SRPX emerges as a non-invasive diagnostic and prognostic biomarker in glioblastoma extracellular vesicles, with expression significantly elevated in temozolomide-resistant tumors; SRPX knockdown inhibits glioblastoma cell viability 6. Additionally, SRPX-2 is differentially secreted on prostate cancer-derived extracellular vesicles in response to nSMase2 inhibition, implicating it in stress-induced EV-mediated cancer progression 7. These findings position SRPX as both a tumor-promoting factor and potential therapeutic target across multiple cancer types.